Pioglitazone acutely stimulates adiponectin secretion from mouse and human adipocytes via activation of the phosphatidylinositol 3'-kinase

Life Sci. 2008 Nov 7;83(19-20):638-43. doi: 10.1016/j.lfs.2008.09.002. Epub 2008 Sep 16.


Aims: Thiazolidinediones increase circulating adiponectin. We have previously demonstrated the involvement of the phosphatidylinositol 3-kinase (PI3K) signaling pathway in insulin-stimulated adiponectin secretion. We therefore investigated the effects of the thiazolidinedione pioglitazone on acute adiponectin secretion, and the involvement of the PI3K signaling pathway in this action.

Main methods: We treated murine 3T3-L1 and human primary adipocytes with 1-10 uM pioglitazone for 2 h, +/-PI3K inhibition by Wortmannin (WT). Secreted adiponectin was measured by Western blot. PI3K activity following 15-minute treatments with 1-10 uM pioglitazone was measured by thin layer chromatography. Pioglitazone's effect on adiponectin synthesis and on secretion of newly synthesized adiponectin was studied in 3T3-L1 adipocytes using a pulse-chase technique.

Key findings: Pioglitazone was found to increase adiponectin secretion and PI3K activity in a dose-dependent manner from 3T3-L1 and human adipocytes. In 3T3-L1 adipocytes, 10 uM pioglitazone increased adiponectin secretion by 84+/-14% (p<0.0001) at 2 h. Similarly, in human adipocytes there was a 56+/-18% (p<0.02) increase in secretion. WT blocked the pioglitazone effect and decreased adiponectin secretion at 2 h (47% of pioglitazone treated, p<0.006). Pioglitazone increased PI3K activity in a dose-dependent manner in both 3T3-L1 (1.7 vs. 2.7-fold increase over control at 2 uM vs. 10 uM dose, p=0.02) and human adipocytes.

Significance: Our data show that pioglitazone acutely stimulates adiponectin secretion from both 3T3-L1 and human adipocytes. This acute effect of pioglitazone is PI3K-dependent.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / drug effects
  • Adipocytes / enzymology
  • Adipocytes / metabolism*
  • Adiponectin / metabolism*
  • Androstadienes / pharmacology
  • Animals
  • Blotting, Western
  • Cell Line
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Enzyme Activation / drug effects
  • Humans
  • Hypoglycemic Agents / pharmacology*
  • Insulin Antagonists / pharmacology
  • Male
  • Mice
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Pioglitazone
  • Thiazolidinediones / pharmacology*
  • Transcription, Genetic
  • Wortmannin


  • Adiponectin
  • Androstadienes
  • Hypoglycemic Agents
  • Insulin Antagonists
  • Thiazolidinediones
  • Phosphatidylinositol 3-Kinases
  • Pioglitazone
  • Wortmannin